4311

MME

membrane metallo-endopeptidase;MME;membrane metallo-endopeptidase

atriopeptidase|common acute lymphocytic leukemia antigen|enkephalinase|membrane metallo-endopeptidase (neutral endopeptidase, enkephalinase)|membrane metallo-endopeptidase (neutral endopeptidase, enkephalinase, CALLA, CD10)|membrane metallo-endopeptidase

3q25.2

protein-coding

CD10 is a cell surface zinc metalloprotease expressed in a variety of normal cell types, including lymphoid precursor cells, germinal centre B lymphocytes and some epithelial cells. The aim of this study was to assess the prognostic value of CD10 in bladder carcinoma. The expression of CD10 was immunohistochemically assessed in 49 cases of primary bladder carcinoma in comparison with 10 non-neoplastic normal bladder mucosa specimens. 27 cases (55%) were tumour CD10(+) and tumour CD10 positivity was significantly correlated with advanced stage, larger tumor size, and shorter mean survival time. Extensive tumoral staining assessed by H score further documented the positive correlation of CD10 with worse prognostic factors in the whole group and its subdivisions (SCC and TCC), in addition to its significant association with bilharziasis in SCC. Only CD10-tumour positivity in the whole group proved to be an independent prognostic factor for overall survival by multivariate analysis. No significant value of stromal CD10 expression in the investigated bladder carcinoma cases was found. This study points to the prognostic value of neoplastic CD10 expression in bladder carcinoma and its possible importance in facilitating tumour invasion and metastasis. Bilharziasis could have a role in upregulation of CD10 expression in SCC.

Identification of prognostic markers in bladder carcinoma comprises a major clinical issue and therapeutic target. CD10 and the adhesion molecule E-cadherin (E-cad) are expressed in a variety of normal tissues and their neoplasms. CD10 is able to degrade extracellular matrix and other proteins, including adhesion molecules. The roles of CD10 and E-cad and their relationship in the development and progression of bladder carcinoma are poorly understood. The aim of this study was to investigate the expression of CD10 and E-cad in bladder carcinomas and relate the results to the established prognostic factors. This study included 144 patients with bladder carcinoma, including 72 with transitional cell carcinoma (TCC; 30 bilharzial and 42 nonbilharzial) and 72 with squamous cell carcinoma (SCC; 38 bilharzial and 34 nonbilharzial). Immunohistochemical analysis for both CD10 and E-cad were carried out on paraffin-fixed sections of neoplastic bladder tissues. CD10 tumor cells, CD10 stromal cells, and E-cad were expressed in 56%, 58%, and 51% of cancer bladder cases, respectively. There was a statistically significant correlation between percentage of tumor cells positively stained by CD10 and each of the tumor grade, clinical stage, and lymph node metastasis of both TCC and SCC. There was a significant statistical correlation between immunostaining by E-cad marker and each of the tumor grade, clinical stage, and lymph node metastasis of TCC, but no such association with SCC. The frequency of stromal expression of CD10 was higher in bilharzial-associated bladder carcinomas than in nonbilharzial ones, and these results were statistically significant. In conclusion, increased expression of CD10 in the tumor and stromal cells of both TCC and SCC and decreased expression of E-cad in the tumor cells of only TCC are strongly correlated with tumor progression, invasion, and metastasis in human bladder cancer.

BACKGROUND: Phyllodes tumors are classified as benign, borderline, and malignant according to a group of histological features. The expression of many biological markers has been explored to discriminate between different grades of phyllodes tumor and to predict their behavior. The immunohistochemical expression of CD10 has been shown to discriminate between benign and other grades of phyllodes tumor but has not been evaluated as a predictor of metastasis. The purpose of this study was to evaluate the usefulness of immunohistochemical staining of stromal CD10 in predicting the likelihood of metastasis in phyllodes tumors. METHODS: The expression of CD10 was studied in 43 phyllodes tumors (16 benign, 10 borderline, and 17 malignant) using immunohistochemistry to evaluate whether differences in expression correlated with the presence of, and or, development of distant metastasis. RESULTS: metastasis occurred in six malignant phyllodes tumors. The expression of CD10 significantly (P<0.05) correlated with the occurrence of distant metastasis. CONCLUSIONS: The expression of CD10 can be used to predict the occurrence of distant metastasis in phyllodes tumors of the breast.

The differential diagnosis between hemangioblastoma of the central nervous system and metastatic clear cell renal cell carcinoma can be problematic, because they may share striking morphologic similarities. Since CD10 is expressed in clear cell renal cell carcinoma, while inhibin alpha is expressed in hemangioblastoma, we used CD10 and inhibin alpha (inhibin A) to study their possible use in the distinction of these two entities. A total of 22 cases of cerebellar hemangioblastoma, five cases of metastatic clear cell renal cell carcinoma to the central nervous system, and 16 primary cases of clear cell renal cell carcinoma were studied with immunohistochemical staining of both CD10 and inhibin A. All 22 cases of hemangioblastoma were immunonegative for CD10 in the stromal cells. In contrast, all five cases of metastatic clear cell renal cell carcinoma and 16 cases of primary clear cell renal cell carcinoma showed positive CD10 membranous staining. In all, 20 cases of hemangioblastoma (20/22, 91%) expressed inhibin A in the stromal cells. Two cases of primary clear cell renal cell carcinoma (2/16, 13%) and three cases of metastatic clear cell renal cell carcinoma (3/5, 60%) showed immunopositivity for inhibin A. In conclusion, in addition to the immunostaining of inhibin A, CD10 is a superior marker for distinguishing between a hemangioblastoma and a metastatic clear cell renal cell carcinoma.

CD10 is a cell surface metalloprotease expressed by a variety of normal cell types, including lymphoid precursor cells, germinal center B lymphocytes, and some epithelial cells. We noticed that stromal cells of some cancers are positive for CD10. In this study, we investigated the role of CD10 produced by the stromal cells of colorectal neoplasms in the progression of colorectal neoplasms. Immunohistochemical examination of CD10 and p53 was performed in 169 colorectal epithelial neoplasms representing various stages of carcinogenesis. The results were correlated with the morphologic characteristics of the neoplasms. There was no expression of CD10 in the stromal cells of normal colorectal tissue. CD10-positive stromal cells were present adjacent to the tumor cells in 16 of 73 adenomas with mild or moderate dysplasia. More frequent expression of CD10 by the stromal cells was detected in adenomas with severe dysplasia (12 of 17), intramucosal carcinomas (10 of 16), and invasive carcinomas (50 of 63) than in adenomas with mild or moderate dysplasia (P < 0.0001). expression of CD10 by > 10% of the stromal cells was detected only within the area of the invasive growth front of invasive carcinomas, not in adenomas and in only 1 of the intramucosal carcinomas. The difference between invasive and non invasive tumors was significant (P < 0.0001). The stromal expression of CD10 was significantly associated with the accumulation of p53 and a larger tumor size. These results indicate that CD10 expression is an integral part of colorectal carcinogenesis. CD10 expression seems to contribute to the invasion and thus probably facilitates metastasis.

CD10 expression is associated with metastases of colorectal cancer (CRC). In the present study, we examined association of CD10 with liver metastasis of CRC cells to clarify the therapeutic significance of CD10. CD10-positive human colon cancer cell line, HT29 cells showed inhibition of growth, invasion and colony formation by treatment with CD10 antisense S-oligodeoxynucleotide (S-ODN). In the mouse liver metastasis mode, CD10 antisense S-ODN-treated HT29 cells made less embedded cells in the liver than control HT29 cells. Number and size of metastatic foci in nude mice liver were reduced in CD10 antisense S-ODN-treated HT29 cells. Treatment with CD10 antisense S-ODN decreased phosphorylation of ERK1/2 and EGFR in HT29 cells. Intraperitoneal administration of liposome-capsulated CD10 antisense S-ODN inhibited establishment of liver metastasis and growth of established metastasis in nude mice. These findings suggest that CD10 is associated substantially with liver metastasis of CRC cells and might be a molecular target of CRC treatment.

BACKGROUND: The risk factors for liver metastasis from colorectal cancer are still unclear. We therefore evaluated the relationships between various clinicopathological factors, including CD10 expression, liver metastasis, and survival, in patients with colorectal cancer. METHODS: Clinicopathological data for 1,025 patients with stage II or III colorectal cancer who underwent curative surgery in four participating hospitals were collected and evaluated. Three pathologists examined focal dedifferentiation, venous invasion, and CD10 expression without knowledge of the clinical outcome. RESULTS: Univariate analysis showed that pathological T (pT), pathological N (pN), venous invasion, focal dedifferentiation, and CD10 expression were significantly associated with liver metastasis. Multivariate analysis selected pT, pN, and CD10 expression as significant risk factors for liver metastasis. pT, pN and CD10 were also shown by univariate and multivariate analyses to be significantly associated with disease-free survival. The incidence of liver metastasis was 3% in pN0 patients with CD10-negative or pT2 or pT3 tumors and 28% in pN2 patients with CD10-positive or pT4 tumors. CONCLUSIONS: CD10 expression is a significant risk factor for liver metastasis in patients with colorectal cancer and is correlated with prognosis. Patients with a high risk of liver metastasis can be selected on the basis of pT, pN, and CD10 expression.

INTRODUCTION: Colorectal cancer (CRC) is the third leading cause of cancer death in Japan. CD10 expression is closely associated with liver metastasis. In the present study, we explored the possibility of serum CD10 as a marker of liver metastasis in CRC. METHODOLOGY: BALB/c mouse with subcutaneous tumor of syngeneic CT26 CRC cells were examined serum CD10. In 84 CRC patients and patients undergoing hemodialysis, serum CD10 was examined. CD10 concentration was measured by enzyme-linked immunosorbent assay. RESULTS: In a mouse subcutaneous tumor model, serum CD10 correlated with the weight of the tumors. Serum CD10 was examined in 84 patients with CRC. The serum levels of CD10 were higher in patients with more advanced cancer stages. Patients with liver metastasis showed the highest levels of serum CD10 among all patients. Importantly, patients with high serum CD10 levels had metachronous liver metastasis. Healthy volunteers showed low levels of CD10; however, serum CD10 levels in patients undergoing hemodialysis showed levels as high as those with stage II and III CRC. A cutoff of serum CD10 set to >1000 pg/mL showed 70% sensitivity and 93% specificity for liver metastasis in CRC. This cutoff included all cases of metachronous liver metastasis. CONCLUSIONS: With the exclusion of mimicking factors, serum CD10 levels might serve as a useful marker of synchronous and metachronous liver metastasis in CRC.

The CD10 antigen is a neutral endopeptidase expressed by a variety of mesenchymal tumours (haemopoietic or not), including a subset of malignant melanomas. We investigated the expression of CD10 in formalin-fixed, paraffin-embedded tissue specimens of 72 cutaneous melanomas (28 primary, 26 metastatic to the skin and 18 lymph node metastases). The CD10 antigen was expressed by 18 of the 26 (69%) and 11 of the 18 (61%) melanomas metastatic to the skin or lymph nodes, respectively; in contrast, only six of the 28 primary melanomas (21.4%) expressed appreciable CD10 reactivity, and expression was usually lower (in terms of the percentage of immunoreactive cells) than that found in metastatic tumours. The sensitivity, specificity, and positive and negative predictive values of CD10 positivity for metastatic malignant melanoma were calculated to be 0.66, 0.79, 0.83 and 0.6, respectively. Our results suggest that the CD10 antigen is upregulated during the process of metastasis in melanomas. From a diagnostic point of view, the expression of CD10 appears to be an additional feature for the histological differential diagnosis between primary and metastatic melanomas.

CD10 antigen is a 100-kDa-cell surface zinc metalloendopeptidase expressed in a variety of normal and neoplastic lymphoid and nonlymphoid tissues including melanomas. It was recently shown that metastatic melanomas express more CD10 than primary tumors. We evaluated CD10 expression in tumor and stromal cells in 70 biopsies with primary and 28 with metastatic malignant melanomas. Ki-67, Bcl-2, and Bax were also examined to investigate whether CD10 expression is associated with tumor proliferation index or factors of apoptosis. Formalin-fixed/paraffin-embedded tissues were studied by immunohistochemistry. More advanced primary tumors had higher CD10 expression in the tumor cells (r = 0.27, P = 0.03 for Clark levels and r = 0.29, P = 0.02 for Breslow) and higher Ki-67 proliferation fraction (r = 0.32, P = 0.007 for Clark levels and r = 0.32, P = 0.001 for Breslow). Similarly, CD10 expression in the intratumoral stromal cells was also higher in primary tumors with higher Clark level (P = 0.04, linear-by-linear association) and tumor thickness according to Breslow (r = 0.33, P = 0.01). The presence of CD10+ peritumoral stromal cell cuffs was also positively associated with tumor thickness according to Breslow (r = 0.27, P = 0.05). Also, expression of CD10 and Ki-67 were significantly higher in metastatic than in primary tumors (P = 0.01 and 0.02 respectively), but Bcl-2 expression was higher in primary melanomas (P = 0.02). We conclude that CD10 expression in malignant melanoma is associated with tumor progression.

OBJECTIVE: To study the expression of neutral endopeptidase (CD10) and motility-related protein-1 (CD9) in malignant melanoma and their clinical significance. METHODS: Immunohistochemical study for CD10 and CD9 using Streptavidin-biotin complex technique was carried out in 48 cases of primary cutaneous malignant melanoma (CMM), 23 cases of metastatic melanoma and 23 cases of benign nevus. RESULTS: The positivity rate of CD10 was highest in metastatic melanoma and lowest in benign nevus (P < 0.01). In contrast, the positivity rate of CD9 in metastatic melanoma was lower than that in CMM (P < 0.05). The expression of CD9 was inversely correlated with that of CD10 in malignant melanoma (CMM: r = -0.40, P = 0.005; metastatic MM: r = -0.44, P = 0.034). The expression of CD10 and CD9 in CMM also correlated with tumor histology, Clark's level of invasion and presence of nodal metastasis. A similar relationship was also observed for CD10 and CD9 expression in stromal fibroblasts of CMM (r = -0.43, P = 0.007). CONCLUSIONS: CD10 and CD9 expression correlates with the invasiveness and metastatic potential of malignant melanoma; both factors may demonstrate a counteracting effect. These two markers have potential implications in prognostic assessment of CMM. Stromal fibroblasts may also play an important role in the progression of CMM.

CD10 is a zinc dependent metallopeptidase, and its expression in stromal and/or epithelial cells of many carcinomas has been suggested to have prognostic value. This study investigates CD10 expression in epithelial and stromal cells of non small cell lung carcinoma (NSCLC), and evaluates its prognostic value for this tumor and its histologic subtypes. Sixty-six cases of NSCLC [35 cases of nonsquamous cell carcinoma (NSCC) and 31 cases of squamous cell carcinoma (SCC)] were analyzed immuno-histochemically for CD10 antibody. Fisher's exact test and univariate survival analyses were performed. Comparison of clinicopathologic characteristics for NSCLC showed that only stromal CD10 expression had worse prognostic impact, associated with the presence of recurrence (p = 0.001), death (p = 0.006) and disease positivity (p = 0.001). For SCC, CD10 was found to be expressed mainly in the stromal cells, and was associated with a decreased survival (p = 0.000) and disease free survival (p = 0.000). CD10 expression was restricted to the epithelial cells in NSCC and associated with an increased disease free survival (p = 0.036). Stromal CD10 expression apppears to be a worse prognostic factor in NSCLCs. CD10 which is expressed in different cell components of SCC and NSCC appears to have opposing effects on the behaviour of these histologic types.

CONTEXT: Recent investigations have demonstrated the utility of CD10 as a marker for renal cell carcinoma (RCC). Cutaneous metastases occur in up to 11% of patients with RCC and may be the presenting sign of widespread disease. The differential diagnosis in histopathologic evaluation of these cases includes cutaneous adnexal neoplasms, and describing the expression of CD10 in these tumors may be helpful in delineating the differential diagnosis. OBJECTIVE: To determine CD10 expression in a variety of adnexal lesions and to determine the diagnostic utility of CD10 in an immunohistochemical panel differentiating metastatic cutaneous renal cell carcinoma from cutaneous adnexal neoplasms. DESIGN: We studied 57 primary adnexal neoplasms of eccrine (n = 31), apocrine (n = 16), and sebaceous (n = 10) differentiation as well as normal skin (n = 3) and RCC metastatic to the skin (n = 4). A CD10 monoclonal antibody was applied to formalin-fixed, paraffin-embedded tissue. Specimens were randomized and categorized as immunopositive or immunonegative by a pathologist with expertise in immunohistochemistry who was blinded to the diagnoses. RESULTS: Two (6.5%) of 31 eccrine, 1 (6%) of 16 apocrine, and 4 (40%) of 10 sebaceous neoplasms demonstrated CD10 immunopositivity. Four (100%) of 4 RCC were CD10 immunopositive. CD10 expression was significant for eccrine and apocrine neoplasms (P < .001) compared to metastatic RCC, but not for sebaceous neoplasms (P = .08). CONCLUSION: Based on these results, CD10 is a useful additional immunostain for the discrimination of RCC metastatic to the skin and cutaneous adnexal neoplasms with eccrine and apocrine differentiation, but not with sebaceous differentiation.

Identification of prognostic markers in bladder carcinoma comprises a major clinical issue and therapeutic target. CD10 and the adhesion molecule E-cadherin (E-cad) are expressed in a variety of normal tissues and their neoplasms. CD10 is able to degrade extracellular matrix and other proteins, including adhesion molecules. The roles of CD10 and E-cad and their relationship in the development and progression of bladder carcinoma are poorly understood. The aim of this study was to investigate the expression of CD10 and E-cad in bladder carcinomas and relate the results to the established prognostic factors. This study included 144 patients with bladder carcinoma, including 72 with transitional cell carcinoma (TCC; 30 bilharzial and 42 nonbilharzial) and 72 with squamous cell carcinoma (SCC; 38 bilharzial and 34 nonbilharzial). Immunohistochemical analysis for both CD10 and E-cad were carried out on paraffin-fixed sections of neoplastic bladder tissues. CD10 tumor cells, CD10 stromal cells, and E-cad were expressed in 56%, 58%, and 51% of cancer bladder cases, respectively. There was a statistically significant correlation between percentage of tumor cells positively stained by CD10 and each of the tumor grade, clinical stage, and lymph node metastasis of both TCC and SCC. There was a significant statistical correlation between immunostaining by E-cad marker and each of the tumor grade, clinical stage, and lymph node metastasis of TCC, but no such association with SCC. The frequency of stromal expression of CD10 was higher in bilharzial-associated bladder carcinomas than in nonbilharzial ones, and these results were statistically significant. In conclusion, increased expression of CD10 in the tumor and stromal cells of both TCC and SCC and decreased expression of E-cad in the tumor cells of only TCC are strongly correlated with tumor progression, invasion, and metastasis in human bladder cancer.